638P - Stereotactic ablative radiotherapy combined with fruquintinib and tislelizumab in metastatic colorectal cancer: Preliminary findings from a single-arm, prospective phase II trial (RIFLE)

Background

Stereotactic ablative radiotherapy (SABR) has been shown to sensitize immunotherapy through inducing immunogenic death and remodeling the tumor immune microenvironment. Anti-angiogenic therapy exhibits synergistic antitumor effects with PD-1/PD-L1 antibodies through its immunomodulatory effects for ≥ 3L metastatic colorectal cancer (mCRC) patients. Here, we report the preliminary results from RIFLE trial: the efficacy and safety of the combination of fruquintinib, PD-1 inhibitor tislelizumab and SABR in mCRC patients.

Methods

This is a single-center, single-arm, prospective phase II clinical trial (NCT04948034). mCRC patients with at least 2 measurable lesions who have failed ≥ 1L standard therapy will receive SABR followed by fruquintinib (5 mg, d1-14, qd) and tislelizumab (200 mg, d1, q3w) within two weeks from completion of radiation. The primary endpoint is the objective response rate (ORR). The secondary endpoints include disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) rate, overall survival (OS) rate and toxicity.

Results

From August 2021 to April 2023, 27 patients were included in the trial and 24 in the efficacy analysis. Median age was 64 years, 17 (70.8%) patients were male, 21(87.5%) had ≥ 3 metastases, and 12(50%) had received ≥ 3 prior lines of systemic therapy. The biological effective dose (BED) for irradiated lesions ranged from 37.5 to 105 Gy. Median study follow-up was 12.6 months, 20 patients were alive and 11 remained on treatment. 7 patients achieved partial response (PR) for target lesions, 10 stable disease (SD), illustrating an ORR of 29.2% and a DCR of 70.8%. Median PFS was not reached. The most common treatment-related adverse events (TRAEs) were proteinuria (45.8%), hypertension (25%) and rash (16.7%). Grade 3-4 AEs occurred in 8 patients, including proteinuria and hypertension, and there were no treatment-related deaths.

Conclusions

SABR combined with tislelizumab and fruquintinib shows promising effects and good safety in the treatment of metastatic colorectal cancer, which is expected to provide new therapeutic strategies and improve the prognosis for mCRC patients.

Clinical trial identification

NCT04948034.

Editorial acknowledgement

Legal entity responsible for the study

Fudan University Shanghai Cancer Center.

Funding

Hutchison MediPharma Co., Ltd. and BeiGene (Beijing) Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.